DESCRIPTION (Applicant's Description): The yeast Candida albicans is found as a commensal organism in the digestive tract of mammals. It is also the most common human fungal pathogen, causing both mucosal and systemic infections, particularly in immunocompromised people. This proposal covers studies of three different aspects of Candida, each of which has been implicated in pathogenesis. These areas are (1) the revesible blostopore to filament morphological transitions, (2) a mechanism to rapidly generate diversity called "phenotypic switching" and (3) the control of features of Candida biology by the MTL locus, a genetic locus closely related to the MAT locus of S. cerevisiae. The proposal also covers the development of two methodologies (large scale genetic screening and microarray analysis of Candida transcription), which, in combination with standard molecular biological and microbiological techniques, will be used to address these problems.